In Vivo Subcutaneous Thermal Video Recording by Supersensitive Infrared Nanothermometers

Abstract

Some of the old and unrealizable dreams of biomedicine have become possible thanks to the appearance of novel advanced materials such as luminescent nanothermometers, nanoparticles capable of providing a contactless thermal reading through their light emission properties. Luminescent nanothermometers have already been demonstrated to be capable of in vivo subcutaneous punctual thermal reading but their real application as diagnosis tools still requires demonstrating their actual capacity for the acquisition of in vivo, time-resolved subcutaneous thermal images. The transfer from 1D to 2D subcutaneous thermal sensing is blocked in the last years mainly due to the lack of high sensitivity luminescent nanothermometers operating in the infrared biological windows. This work demonstrates how core/shell engineering, in combination with selective rare earth doping, can be used to develop supersensitive infrared luminescent nanothermometers. Erbium, thulium, and ytterbium core-shell LaF 3 nanoparticles, operating within the biological windows, provide thermal sensitivities as large as 5% °C −1 . This "record" sensitivity has allowed for the final acquisition of subcutaneous thermal videos of a living animal. Subsequent analysis of thermal videos allows for an unequivocal determination of intrinsic properties of subcutaneous tissues, opening the venue to the development of novel thermal imaging-based diagnosis tools.

Integrating Positive and Negative Thermal Quenching Effect for Ultrasensitive Ratiometric Temperature Sensing and Anti-counterfeiting

“…A similar negative thermal quenching effect has also been reported in the Yb/Er, 26,37 Yb/Ho, 44 and Yb/Tm 44 codoped fluoride nanosystems, which probably attributed to the enhanced surface phonon-assisted energy-transfer efficiency from sensitizers to activators or decreased energy migration possibility from activators to surface defects at high temperatures. Because the negative thermal quenching effect is highly related to the NC surface, it is highly desirable to use a shell layer to prevent the surface effect on the activators.…”

Integrating Positive and Negative Thermal Quenching Effect for Ultrasensitive Ratiometric Temperature Sensing and Anti-counterfeiting

“…A similar negative thermal quenching effect has also been reported in the Yb/Er, 26,37 Yb/Ho, 44 and Yb/Tm 44 codoped fluoride nanosystems, which probably attributed to the enhanced surface phonon-assisted energy-transfer efficiency from sensitizers to activators or decreased energy migration possibility from activators to surface defects at high temperatures. Because the negative thermal quenching effect is highly related to the NC surface, it is highly desirable to use a shell layer to prevent the surface effect on the activators.…”

Luminescent Nanothermometer Operating at Very High Temperature—Sensing up to 1000 K with Upconverting Nanoparticles (Yb3+/Tm3+)

“…In the presented comparison, there are only few reports showing significantly higher S r max values (up to 9% K –1 ), however, these values were obtained at very low (cryogenic) temperature values. Obviously, there are some other reports showing luminescent thermometers with similar or higher S r values but they operate in a low- or mild-temperature range. , On the other hand, there is no doubt that in a very high-temperature range, we achieved the highest S r (2.13% K –1 at 1009 K), compared to other reports, where sensitivity significantly decreases with temperature, and the S r values are very low in the range of 800–1000 K, that is, usually around 0.3–0.1% K –1 (see Table ). Please note that the temperature resolution (δ T ) is not given in the presented comparison because the vast majority of researchers do not report on this parameter, especially in the high-temperature region.…”

Lanthanide Upconverted Luminescence for Simultaneous Contactless Optical Thermometry and Manometry–Sensing under Extreme Conditions of Pressure and Temperature

“…Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. 2 , 31 , 33 The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure 3 e.…”

“…It can be clearly seen that the relative intensity of the thermalized 2 H 11/2 → 4 I 15/2 transition at ∼525 nm increases significantly with temperature compared to other bands of Er 3+ . On the other hand, the band intensities at ∼545 and ∼660 nm decrease, as observed in Figure S10, due to thermal quenching processes, such as enhanced multiphonon relaxation and, in the case of the 4 S 3/2 → 4 I 15/2 transition, the mentioned thermalization processes. ,, Thanks to the thermally coupled nature of the 2 H 11/2 and 4 S 3/2 energy levels in Er 3+ ions, the corresponding band intensity ratio 2 H 11/2 → 4 I 15/2 / 4 S 3/2 → 4 I 15/2 (525/545 nm) is commonly used for optical temperature sensing purposes. ,− ,,, In other words, elevation of temperature increases the population of the 2 H 11/2 multiplet and at the same time decreases the population of the 4 S 3/2 multiplet. These processes are consistent with the Boltzmann type distribution: where LIR is the luminescence intensity ratio or band ratio; Δ E is the energy difference between the centroids of the 2 H 11/2 → 4 I 15/2 and 4 S 3/2 → 4 I 15/2 emission bands; I 525 and I 545 are their integrated intensities, respectively; k B is the Boltzmann constant; T is the absolute temperature; and B is a constant, associated with the state degeneracies, branching ratio of the transitions in relation to the ground state, energy of the transitions, and rates of total spontaneous emission …”

“…Additionally, we determined the band intensity ratio of the nonthermally coupled levels (non-TCLs) 2 H 11/2 → 4 I 15/2 / 4 F 9/2 → 4 I 15/2 (525/660 nm), and fitted it to the second-order polynomial function: LIR = −4.14 × 10 –7 T 2 + 8.94 × 10 –4 T −0.18, with R 2 ≈0.994 (Figure d), as they do not conform to the Boltzmann distribution. Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. ,, The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure e.…”

Integrating Positive and Negative Thermal Quenching Effect for Ultrasensitive Ratiometric Temperature Sensing and Anti-counterfeiting

“…A similar negative thermal quenching effect has also been reported in the Yb/Er, 26,37 Yb/Ho, 44 and Yb/Tm 44 codoped fluoride nanosystems, which probably attributed to the enhanced surface phonon-assisted energy-transfer efficiency from sensitizers to activators or decreased energy migration possibility from activators to surface defects at high temperatures. Because the negative thermal quenching effect is highly related to the NC surface, it is highly desirable to use a shell layer to prevent the surface effect on the activators.…”

Luminescent Nanothermometer Operating at Very High Temperature—Sensing up to 1000 K with Upconverting Nanoparticles (Yb3+/Tm3+)

“…In the presented comparison, there are only few reports showing significantly higher S r max values (up to 9% K –1 ), however, these values were obtained at very low (cryogenic) temperature values. Obviously, there are some other reports showing luminescent thermometers with similar or higher S r values but they operate in a low- or mild-temperature range. , On the other hand, there is no doubt that in a very high-temperature range, we achieved the highest S r (2.13% K –1 at 1009 K), compared to other reports, where sensitivity significantly decreases with temperature, and the S r values are very low in the range of 800–1000 K, that is, usually around 0.3–0.1% K –1 (see Table ). Please note that the temperature resolution (δ T ) is not given in the presented comparison because the vast majority of researchers do not report on this parameter, especially in the high-temperature region.…”

Lanthanide Upconverted Luminescence for Simultaneous Contactless Optical Thermometry and Manometry–Sensing under Extreme Conditions of Pressure and Temperature

“…Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. 2 , 31 , 33 The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure 3 e.…”

“…It can be clearly seen that the relative intensity of the thermalized 2 H 11/2 → 4 I 15/2 transition at ∼525 nm increases significantly with temperature compared to other bands of Er 3+ . On the other hand, the band intensities at ∼545 and ∼660 nm decrease, as observed in Figure S10, due to thermal quenching processes, such as enhanced multiphonon relaxation and, in the case of the 4 S 3/2 → 4 I 15/2 transition, the mentioned thermalization processes. ,, Thanks to the thermally coupled nature of the 2 H 11/2 and 4 S 3/2 energy levels in Er 3+ ions, the corresponding band intensity ratio 2 H 11/2 → 4 I 15/2 / 4 S 3/2 → 4 I 15/2 (525/545 nm) is commonly used for optical temperature sensing purposes. ,− ,,, In other words, elevation of temperature increases the population of the 2 H 11/2 multiplet and at the same time decreases the population of the 4 S 3/2 multiplet. These processes are consistent with the Boltzmann type distribution: where LIR is the luminescence intensity ratio or band ratio; Δ E is the energy difference between the centroids of the 2 H 11/2 → 4 I 15/2 and 4 S 3/2 → 4 I 15/2 emission bands; I 525 and I 545 are their integrated intensities, respectively; k B is the Boltzmann constant; T is the absolute temperature; and B is a constant, associated with the state degeneracies, branching ratio of the transitions in relation to the ground state, energy of the transitions, and rates of total spontaneous emission …”

“…Additionally, we determined the band intensity ratio of the nonthermally coupled levels (non-TCLs) 2 H 11/2 → 4 I 15/2 / 4 F 9/2 → 4 I 15/2 (525/660 nm), and fitted it to the second-order polynomial function: LIR = −4.14 × 10 –7 T 2 + 8.94 × 10 –4 T −0.18, with R 2 ≈0.994 (Figure d), as they do not conform to the Boltzmann distribution. Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. ,, The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure e.…”

Integrating Positive and Negative Thermal Quenching Effect for Ultrasensitive Ratiometric Temperature Sensing and Anti-counterfeiting

“…A similar negative thermal quenching effect has also been reported in the Yb/Er, 26,37 Yb/Ho, 44 and Yb/Tm 44 codoped fluoride nanosystems, which probably attributed to the enhanced surface phonon-assisted energy-transfer efficiency from sensitizers to activators or decreased energy migration possibility from activators to surface defects at high temperatures. Because the negative thermal quenching effect is highly related to the NC surface, it is highly desirable to use a shell layer to prevent the surface effect on the activators.…”

Luminescent Nanothermometer Operating at Very High Temperature—Sensing up to 1000 K with Upconverting Nanoparticles (Yb3+/Tm3+)

“…In the presented comparison, there are only few reports showing significantly higher S r max values (up to 9% K –1 ), however, these values were obtained at very low (cryogenic) temperature values. Obviously, there are some other reports showing luminescent thermometers with similar or higher S r values but they operate in a low- or mild-temperature range. , On the other hand, there is no doubt that in a very high-temperature range, we achieved the highest S r (2.13% K –1 at 1009 K), compared to other reports, where sensitivity significantly decreases with temperature, and the S r values are very low in the range of 800–1000 K, that is, usually around 0.3–0.1% K –1 (see Table ). Please note that the temperature resolution (δ T ) is not given in the presented comparison because the vast majority of researchers do not report on this parameter, especially in the high-temperature region.…”

Lanthanide Upconverted Luminescence for Simultaneous Contactless Optical Thermometry and Manometry–Sensing under Extreme Conditions of Pressure and Temperature

“…Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. 2 , 31 , 33 The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure 3 e.…”

“…It can be clearly seen that the relative intensity of the thermalized 2 H 11/2 → 4 I 15/2 transition at ∼525 nm increases significantly with temperature compared to other bands of Er 3+ . On the other hand, the band intensities at ∼545 and ∼660 nm decrease, as observed in Figure S10, due to thermal quenching processes, such as enhanced multiphonon relaxation and, in the case of the 4 S 3/2 → 4 I 15/2 transition, the mentioned thermalization processes. ,, Thanks to the thermally coupled nature of the 2 H 11/2 and 4 S 3/2 energy levels in Er 3+ ions, the corresponding band intensity ratio 2 H 11/2 → 4 I 15/2 / 4 S 3/2 → 4 I 15/2 (525/545 nm) is commonly used for optical temperature sensing purposes. ,− ,,, In other words, elevation of temperature increases the population of the 2 H 11/2 multiplet and at the same time decreases the population of the 4 S 3/2 multiplet. These processes are consistent with the Boltzmann type distribution: where LIR is the luminescence intensity ratio or band ratio; Δ E is the energy difference between the centroids of the 2 H 11/2 → 4 I 15/2 and 4 S 3/2 → 4 I 15/2 emission bands; I 525 and I 545 are their integrated intensities, respectively; k B is the Boltzmann constant; T is the absolute temperature; and B is a constant, associated with the state degeneracies, branching ratio of the transitions in relation to the ground state, energy of the transitions, and rates of total spontaneous emission …”

“…Additionally, we determined the band intensity ratio of the nonthermally coupled levels (non-TCLs) 2 H 11/2 → 4 I 15/2 / 4 F 9/2 → 4 I 15/2 (525/660 nm), and fitted it to the second-order polynomial function: LIR = −4.14 × 10 –7 T 2 + 8.94 × 10 –4 T −0.18, with R 2 ≈0.994 (Figure d), as they do not conform to the Boltzmann distribution. Please note that despite the fact that there is no thermalization between these two bands, they apparently exhibit different temperature-dependent quenching and energy transfer rates; hence they can be correlated with temperature and used for sensing purposes. ,, The calculated S r values for the 525/660 nm band ratios decrease from ≈1.4% K –1 (at 295 K) down to ≈0.3% K –1 (at 478 K), as observed in Figure e.…”